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Frontiers in Immunology 2019Vitamin A deficiencies and insufficiencies are widespread in developing countries, and may be gaining prevalence in industrialized nations. To combat vitamin A...
Vitamin A deficiencies and insufficiencies are widespread in developing countries, and may be gaining prevalence in industrialized nations. To combat vitamin A deficiency (VAD), the World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) in children 6-59 months of age in locations where VAD is endemic. This practice has significantly reduced all-cause death and diarrhea-related mortalities in children, and may have in some cases improved immune responses toward pediatric vaccines. However, VAS studies have yielded conflicting results, perhaps due to influences of baseline vitamin A levels on VAS efficacy, and due to cross-regulation between vitamin A and related nuclear hormones. Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases. We additionally present new results from a VAD mouse model. We found that when VAS was administered to VAD mice at the time of vaccination with a pneumococcal vaccine (Prevnar-13), pneumococcus (T4)-specific antibodies were significantly improved. Preliminary data further showed that after challenge with , all mice that had received VAS at the time of vaccination survived. This was a significant improvement compared to vaccination without VAS. Data encourage renewed attention to vitamin A levels, both in developed and developing countries, to assist interpretation of data from vaccine research and to improve the success of vaccine programs.
Topics: Animals; Dietary Supplements; Female; Immunogenicity, Vaccine; Male; Mice; Mice, Inbred C57BL; Pneumococcal Vaccines; Pregnancy; Vaccination; Vitamin A; Vitamin A Deficiency
PubMed: 31379816
DOI: 10.3389/fimmu.2019.01576 -
Cellular and Molecular Gastroenterology... 2021
Topics: Humans; Non-alcoholic Fatty Liver Disease; Vitamin A
PubMed: 32971038
DOI: 10.1016/j.jcmgh.2020.08.007 -
International Journal of Molecular... Dec 2023Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these... (Review)
Review
Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.
Topics: Humans; Vitamin A; Matrix Metalloproteinase 2; Vitamins; Vitamin K; Cardiovascular Diseases; Vitamin D; Vitamin E
PubMed: 38069361
DOI: 10.3390/ijms242317038 -
Journal of Cancer Research and Clinical... May 2023Vitamin A and its derivatives positively influence the differentiation of epithelia and other tissues and prevent the proliferation of preneoplastic and neoplastic... (Review)
Review
PURPOSE
Vitamin A and its derivatives positively influence the differentiation of epithelia and other tissues and prevent the proliferation of preneoplastic and neoplastic cells. Vitamin A is therefore taken into account as a potential supporting factor in cancer therapy.
METHODS
In November 2020, a systematic search was conducted searching five electronic databases (EMBASE, Cochrane, PsycINFO, CINAHL and Medline) to find studies looking at the effects of using vitamin A as a complementary therapy for cancer patients. From all 12,823 search results, 9 publications referring to 9 studies with 4296 patients were included in this systematic review.
RESULTS
The patients treated with vitamin A were diagnosed with various cancers and stages. Outcome variables were overall survival of cancer, progression-free survival, occurrence of second primary tumours and recurrences, improvement of chronic radiation-induced proctopathy and side effects of vitamin A. For the most part, the studies had a limited methodological quality. In summary, it can be said that due to the methodological deficiencies of the studies, no concrete statement can be made regarding the prolongation of overall survival and progression-free survival. There is also no evidence of the benefit of vitamin A in the treatment of chronic radiation-induced proctopathy, which can be attributed to methodological deficiencies in the study, as well. In the studies that report on side effects, it becomes clear that side effects, such as mucocutaneous symptoms, temporary increase in liver enzymes and gastrointestinal side effects occur more frequently in the group with vitamin A intervention.
CONCLUSION
The limited interpretability of the results due to the methodological deficiencies of the included studies does not allow a final statement on the benefits of vitamin A as a complementary treatment for cancer patients.
Topics: Humans; Vitamin A; Neoplasms
PubMed: 35972692
DOI: 10.1007/s00432-022-04224-6 -
BMJ Global Health Jul 2020WHO recommends vitamin A supplementation (VAS) programmes for children 6-59 months where vitamin A deficiency is a public health problem. However, resources for VAS are... (Review)
Review
WHO recommends vitamin A supplementation (VAS) programmes for children 6-59 months where vitamin A deficiency is a public health problem. However, resources for VAS are falling short of current needs and programme coverage is suffering. The authors present the case for considering the options for shifting efforts and resources from a generalised approach, to prioritising resources to reach populations with continued high child mortality rates and high vitamin A deficiency prevalence to maximise child survival benefits . This includes evaluating where child mortality and/or vitamin A deficiency has dropped, as well as using under 5 mortality rates as a proxy for vitamin A deficiency, in the absence of recent data. The analysis supports that fewer countries may now need to prioritise VAS than in the year 2000, but that there are still a large number of countries that do. The authors also outline next steps for analysing options for improved targeting and cost-effectiveness of programmes. Focusing VAS resources to reach the most vulnerable is an efficient use of resources and will continue to promote young child survival.
Topics: Child; Cost-Benefit Analysis; Dietary Supplements; Humans; Prevalence; Vitamin A; Vitamin A Deficiency; Vulnerable Populations
PubMed: 32718947
DOI: 10.1136/bmjgh-2019-001997 -
The Journal of Biological Chemistry Sep 2021Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for...
Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D-vitamin A.
Topics: Aging; Animals; Dark Adaptation; Eye; Humans; Macular Degeneration; Male; Mice; Mice, Inbred ICR; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Visual Acuity; Vitamin A
PubMed: 34391781
DOI: 10.1016/j.jbc.2021.101074 -
Translational Psychiatry Feb 2023The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in...
The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.
Topics: Male; Humans; Female; Retinoids; Depressive Disorder, Major; Leukocytes, Mononuclear; Tretinoin; Vitamin A; Homeostasis
PubMed: 36813763
DOI: 10.1038/s41398-023-02362-0 -
Nutrients Apr 2022The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells,... (Review)
Review
The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.
Topics: Animals; HIV Infections; Humans; Immunity, Mucosal; Tretinoin; Virus Replication; Vitamin A
PubMed: 35458172
DOI: 10.3390/nu14081611 -
Biochimica Et Biophysica Acta.... Nov 2020Atherosclerotic cardiovascular disease (ASCVD) is the principal contributor to myocardial infarction, the leading cause of death worldwide. Epidemiological and... (Review)
Review
Atherosclerotic cardiovascular disease (ASCVD) is the principal contributor to myocardial infarction, the leading cause of death worldwide. Epidemiological and mechanistic studies indicate that β-carotene and its vitamin A derivatives stimulate lipid catabolism in several tissues to reduce the incidence of obesity, but their roles within ASCVD are elusive. Herein, we review the mechanisms by which β-carotene and vitamin A modulate ASCVD. First, we summarize the current knowledge linking these nutrients with epidemiological studies and lipoprotein metabolism as one of the initiating factors of ASCVD. Next, we focus on different aspects of vitamin A metabolism in immune cells such as the mechanisms of carotenoid uptake and conversion to the vitamin A metabolite, retinoic acid. Lastly, we review the effects of retinoic acid on immuno-metabolism, differentiation, and function of macrophages and T cells, the two pillars of the innate and adaptive immune response in ASCVD, respectively. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
Topics: Atherosclerosis; Biological Transport; Humans; Lipid Metabolism; Macrophages; Obesity; Vitamin A; beta Carotene
PubMed: 31978554
DOI: 10.1016/j.bbalip.2020.158635 -
Eye (London, England) May 2023Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT,...
BACKGROUND
Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT, this study aimed to characterize and follow a novel retinal abnormality in patients with VAD and intramuscular supplementation.
METHODS
Patients with VAD were retrospectively reviewed, including SD-OCT and electroretinography.
RESULTS
Three patients had VAD following bariatric or colon surgery and varying supplementation. All had nyctalopia, extinguished scotopic rod-specific function with ERG, and decreased serum vitamin A. None demonstrated surface abnormalities. All received intramuscular vitamin A with subjective resolution of symptoms. On SD-OCT, four of six eyes exhibited homogenous foveal hyperreflectivity anterior to retinal pigment epithelium-Bruch complex, reminiscent of a "double carrot", which improved following supplementation. ERG findings demonstrated improved scotopic rod-specific function in all cases; however, photopic function remained diminished in two cases.
CONCLUSIONS
Structural improvement of the proposed "double carrot" sign occurs soon after vitamin A supplementation. While scotopic function improves rapidly following supplementation, cone function recovers more slowly. Therefore, foveal changes such as the "double carrot" sign suggest that structural recovery of cones precedes functional recovery.
Topics: Humans; Electroretinography; Retina; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Vitamin A; Vitamin A Deficiency
PubMed: 35840717
DOI: 10.1038/s41433-022-02137-9